CARBAMAZEPINE AFFECTS NEUTROPHIL FUNCTION THROUGH AN ACTION ON PERIPHERAL BENZODIAZEPINE RECEPTORS

The aims of this study were to assess the possible role of peripheral benzodiazepine receptors (pBZrs)(1) in mediating the in vitro effects of carbamazepine (CBZ) on some neutrophil functions in healthy volunte ers and to investigate neutrophil function and pBZr expression in pati ents with epilepsia on CBZ monotherapy for at least 1 year. In vitro C BZ (42-168 mu M) concentration-dependently inhibited chemotaxis induce d by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or lipopolysacchar ide (LPS)-activated human serum. CBZ did not affect random migration, phagocytosis index, phagocytosis frequency, NBT reduction frequency, C . albicans lethality index and resting superoxide production. The pBZr antagonist PK 11195 (1 mu M, per se ineffective) reversed the inhibit ory effect of CBZ on chemotaxis induced by endotoxin-activated serum o r FMLP. The pBZr agonist Ro 5-4864 (10-100 mu M) mimicked the effect o f CBZ on chemotaxis induced by endotoxin-activated serum or FMLP and h ad no effect on the other parameters. Neutrophils from epileptic patie nts on chronic CBZ monotherapy had impaired FMLP- and serum-induced ch emotaxis and enhanced expression of pBZrs on neutrophils. These data s trongly suggest an involvement of pBZrs in mediating the in vitro effe cts of CBZ on chemotaxis; furthermore, impairment of the same neutroph il function parameters and overexpression of pBZrs in patients are con sistent with the hypothesis of an in vivo interaction of CBZ with pBZr s.